For example, the U.S. Pat. No. 4,258,058 discloses Sulotroban represented by the following formula and its derivatives: ##STR2## and the U.S. Pat. No. 4,443,477 discloses Daltroban represented by the following formula and its derivatives: ##STR3## as benzenesulfonamide derivatives having thromboxane A.sub.2 antagonistic activity. However, compounds structurally similar to the compounds of the present invention have never been known so far.
Thromboxane A.sub.2 is a potent physiologically active substance which is biosynthesized from arachidonic acid in living bodies. The substance has platelet aggregation activity and contracting activity on smooth muscles such as bronchi and coronary arteries. Although the substance is rather important in living bodies, it is considered that its excessive production may cause various disorders such as thrombosis and asthma. Leucotriene is also a potent physiologically active substance biosynthesized from arachidonic acid. This substance induces various pharmacological effects such as contraction of respiratory tract smooth muscle, hyper-secretion of respiratory tract and hyper-permeation of blood vessels, and is considered to be significantly involved in pathopoiesis of asthma and allergic inflammation.
For these reasons, drugs having thromboxane A.sub.2 antagonistic activity are expected to be useful as preventive and therapeutic agents for diseases associated with thromboxane A.sub.2 such as, for example, ischemic heart diseases such as angina pectoris and myocardial infarction, cerebrovascular diseases, thrombosis, and asthma. Drugs having leucotriene antagonistic activity are also expected to be useful as preventive and therapeutic agents for diseases associated with leucotriene such as, for example, asthma and allergic inflammation. Although several thromboxane A.sub.2 antagonists and leucotriene antagonists have been under clinical trials, they are not commercially available at present. Accordingly, further researches have been desired.
An object of the present invention is thus to provide medicaments having thromboxane A.sub.2 antagonistic activity and leucotriene antagonistic activity and useful as drugs for preventive and therapeutic treatments for ischemic heart diseases such as angina pectoris and myocardial infarction, cerebrovascular diseases, thrombosis, and asthma, or useful as drugs for preventive and therapeutic treatments for asthma and allergic inflammation.
The inventors of the present invention conducted various studies under these circumstances and, as a result, found that the novel benzenesulfonamide derivatives of the present invention have inhibitory activities against thromboxane A.sub.2 synthetase in addition to thromboxane A.sub.2 antagonistic activities and leucotriene D.sub.4 antagonistic activities. The inventors also found that they are highly useful as platelet aggregation inhibitors, antithrombotic agents, antiasthmatic agents and antiallergic agents. The present invention was achieved on the basis of these findings.